本文選題：食管鱗狀細胞癌　切入點：微小RNA-195　出處：《新鄉(xiāng)醫(yī)學院》2015年碩士論文

【摘要】：背景食管癌是常見的消化系統(tǒng)惡性腫瘤,發(fā)病率高,5年生存率低,僅15%左右,河南省安陽林州及周邊地區(qū)是中國也是世界食管癌發(fā)病率最高的地區(qū)。在臨床工作中,確定食管癌的臨床結局主要參考臨床病理特征,如TNM分期等。但是在大規(guī)模流行病調查工作中發(fā)現(xiàn)TNM分期并不能準確的預測患者的預后,所以尋找能夠預測食管癌預后的生物標志物具有重要意義。細胞分裂周期蛋白42(Cell division cycle protein 42,Cdc42)是微小RNA-195 (MicroRNA-195,miR-195)的靶基因,研究發(fā)現(xiàn)miR-195、 Cdc42可能參與了食管癌的發(fā)生過程,但在人類食管癌組織中的表達及其臨床意義尚不清楚。目的探討miR-195、Cdc42在食管癌組織中的表達與預后的相關性,旨在探討二者作為食管癌預后評價生物標志物的可能性。方法1.研究對象：571例行根治切除手術的原發(fā)性食管癌患者均來自河南省豫北地區(qū)某三級甲等醫(yī)院,患者臨床病理資料完整、術中病理標本保存完好者,通過隨訪明確患者術后生存時間(隨訪時間截止到2013年12月)。隨訪期間所進行的檢查包括食管造影,CT掃描及骨掃描等以及時發(fā)現(xiàn)復發(fā)和或轉移。隨訪間隔時間第1年每3個月1次,第2年每6個月1次。隨機抽取98例作為研究對象。2.實驗方法：入選患者術中病理組織標本(既往收集的術中新鮮病理組織標本冷凍保存于_80℃冰箱中),HE染色確定組織病理類型；應用Taqman熒光定量PCR(qRT-PCR)法檢測miR-195和Cdc42在食管癌組織、癌旁組織及正常食管組織中的表達。運用χ2檢驗分析miR-195、Cdc42的表達與臨床病理特征的關系,運用Kaplan-Meier生存分析、Cox比例風險模型等進行預后分析。結果1.HE染色結果顯示：98例為食管鱗狀細胞癌；98例為食管癌旁組織；10例為正常食管組織。2. qRT-PCR檢測結果顯示：miR-195在食管癌組織中相對表達含量與癌旁組織和正常食管組織比較顯著下調(P0.001)；Cdc42在食管癌組織中相對表達含量與癌旁組織和正常食管組織比較顯著上調(P0.001)；Spearman相關分析顯示：miR-195和Cdc42的表達水平呈負相關(P0.001)。3.miR-195的低表達與TNM分期和淋巴結轉移顯著相關(P0.05)；Cdc42的高表達與TNM分期和腫瘤分化程度顯著相關(P0.05)。4. Kaplan-Meier生存分析顯示：Low-miR-195組或High-Cdc42組患者的總生存期(OS)和無進展生存期(PFS)短于High-miR-195組或Low-Cdc42組(P0.001)；Low-miR-195/High-Cdc42同時表達時OS和PFS較短,按照OS和PFS從長到短依次為High-miR-195/Low-Cdc42、High-miR-195/High-Cdc42、Low-miR-195 /Low-Cdc42、Low-miR-195/High-Cdc42。5.Cox比例風險模型多因素分析顯示：TNM分期、腫瘤分化、淋巴結轉移、Low-miR-195、High-Cdc42或Low-miR-195/High-Cdc42同時表達等是影響食管癌患者OS和PFS的獨立危險因素(P0.05)。結論食管癌組織中miR-195表達下調、Cdc42表達上調、Low-miR-195/High-Cdc42同時表達等均提示預后不良,是食管癌患者預后不良的獨立危險因素。miR-195、Cdc42可作為食管癌預后評價的生物標志物。
[Abstract]:Background: esophageal cancer is the common malignant tumor of digestive system, high incidence rate, 5 year survival rate is low, only about 15%, Henan Province, Anyang, Linzhou and the surrounding area is also China esophageal cancer in the world. The highest rate in the clinical work, the main parameters determining outcome of esophageal cancer clinical pathological features, such as TNM stage. But find prognostic staging in patients with TNM was not accurate in large-scale epidemiological survey work, so the search for biomarkers to predict the prognosis of esophageal cancer has important significance. The cell cycle protein 42 (Cell division cycle protein 42, Cdc42) is a small RNA-195 (MicroRNA-195, miR-195) of the target gene, research the discovery of miR-195, Cdc42 may participate in the process of esophageal cancer, but the expression in human esophageal carcinoma and its clinical significance is unclear. Objective to investigate the effect of miR-195, Cdc42 in esophageal cancer group The relationship between the expression and prognosis in fabric, aims to explore the two as the prognosis of esophageal cancer biomarker evaluation possibilities. Methods 1. subjects: 571 cases underwent radical resection of primary esophageal cancer patients from the northern area of Henan Province, a three grade hospital, clinical pathological data were complete, well preserved pathology specimens during the operation, the survival time of the patients with postoperative follow-up clear (follow-up until December 2013). The follow-up examination included esophageal radiography, CT scan and bone scan and found recurrence and / or metastasis. The follow-up interval of first years every 3 months for 1 times, second years every 6 months for 1 times. 98 patients were randomly selected as the research object.2. methods: selected patients with pathological tissue specimens (previously collected in the operation of fresh tissue cryopreservation at _80 deg.c in the refrigerator), HE staining to determine the tissue pathological types ; application of Taqman fluorescence quantitative PCR (qRT-PCR) was used to detect miR-195 and Cdc42 expression in esophageal cancer tissue, adjacent tissues and normal esophageal tissues. Using 2 test analysis of miR-195, the relationship between Cdc42 expression and clinicopathological features, prognosis by Kaplan-Meier survival analysis, Cox proportional hazards regression model. The results of 1.HE staining results: 98 cases of esophageal squamous cell carcinoma; 98 cases of esophageal cancer; 10 cases of normal esophageal tissue.2. qRT-PCR test results show that: miR-195 in esophageal carcinoma and the relative expression content in adjacent tissues and normal esophageal tissue significantly decreased (P0.001); Cdc42 in human esophageal carcinoma tissues, the relative expression content with the adjacent tissues and normal esophageal tissue increased significantly (P0.001); Spearman correlation analysis showed that the expression level of miR-195 was negatively related to Cdc42 and the low expression of.3.miR-195 (P0.001) With TNM staging and lymph node metastasis was significantly correlated (P0.05); and the high expression of TNM was significantly related to Cdc42 staging and tumor differentiation (P0.05).4. Kaplan-Meier survival analysis showed that overall survival in Low-miR-195 group or High-Cdc42 group (OS) and progression free survival (PFS) was shorter than that of group High-miR-195 or group Low-Cdc42 (P0.001; Low-miR-195/High-Cdc42) expression of OS and PFS at the same time is short, according to OS and PFS from long to short sequence of High-miR-195/Low-Cdc42, High-miR-195/High-Cdc42, Low-miR-195, /Low-Cdc42, multivariate Low-miR-195/High-Cdc42.5.Cox proportional risk model analysis showed that TNM stage, tumor differentiation, lymph node metastasis, Low-miR-195, High-Cdc42 or Low-miR-195/High-Cdc42 at the same time, the expression is independent risk and OS PFS factors in patients with esophageal cancer (P0.05). Conclusion the expression of miR-195 in esophageal cancer tissues, Cdc42 expression, Low-miR-195/ High-Cdc42 expression at the same time indicates poor prognosis. It is an independent risk factor for poor prognosis of esophageal cancer..miR-195 and Cdc42 can be used as biomarkers for prognosis evaluation of esophageal cancer.

【學位授予單位】：新鄉(xiāng)醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.1

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本文編號：1688410